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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Interaction of Platinum-based Drugs with Proteins: An Overview of Representative Crystallographic Studies

Author(s): Giarita Ferraro, Domenico Loreto and Antonello Merlino*

Volume 21, Issue 1, 2021

Published on: 24 June, 2020

Page: [6 - 27] Pages: 22

DOI: 10.2174/1568026620666200624162213

Price: $65

Abstract

Pt-based drugs are widely used in clinics for the treatment of cancer. The mechanism of action of these molecules relies on their interaction with DNA. However, the recognition of these metal compounds by proteins plays an important role in defining pharmacokinetics, side effects and their overall pharmacological profiles. Single crystal X-ray diffraction studies provided important information on the molecular mechanisms at the basis of this process. Here, the molecular structures of representative adducts obtained upon reaction with proteins of selected Pt-based drugs, including cisplatin, carboplatin and oxaliplatin, are briefly described and comparatively examined. Data indicate that metal ligands play a significant role in driving the reaction of Pt compounds with proteins; non-covalent interactions that occur in the early steps of Pt compound/protein recognition process play a crucial role in defining the structure of the final Pt-protein adduct. In the metallated protein structures, Pt centers coordinate few protein side chains, such as His, Met, Cys, Asp, Glu and Lys residues upon releasing labile ligands.

Keywords: Protein metalation, Cisplatin analogues, Protein-metallodrug interactions, Metal-based drugs, X-ray crystallography, Metal-protein adducts.

Graphical Abstract
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